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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05627323
Other study ID # CHM-1101-001
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date June 6, 2023
Est. completion date January 2041

Study information

Verified date November 2023
Source Chimeric Therapeutics
Contact Chimeric Therapeutics
Phone 1-866-430-1081
Email clinicaltrials@chimerictherapeutics.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).


Description:

This is a phase 1b, multicenter, feasibility/safety study of the dual delivery (administered through both intracavitary/intratumoral [ICT] and intraventricular [ICV] catheters) of CHM-1101, an autologous chlorotoxin-chimeric antigen receptor (CLTX-CAR) cell product, in participants with recurrent or progressive GBM. The investigational product is identified as CHM-1101 (CLTX(EQ)28ζ/CD19t+ CAR T cells). PRIMARY OBJECTIVE • To determine the recommended phase 2 dose (RP2D) for dual ICT and ICV delivery of CHM-1101 in participants with MMP2+ recurrent or progressive GBM. SECONDARY OBJECTIVES - To assess the feasibility and safety of dual delivery of CHM-1101. - To describe the persistence, expansion, immunogenicity, and phenotype of CHM-1101 and endogenous cells tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF). - In participants who receive at least 2 of the 3 planned doses of CHM-1101 in Cycle 1: - Estimate the progression-free survival (PFS) rates - Estimate the overall survival (OS) rates - To evaluate the disease response rate.


Recruitment information / eligibility

Status Recruiting
Enrollment 42
Est. completion date January 2041
Est. primary completion date October 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Documented informed consent of the subject and/or legally authorized representative. - Agreement to allow the use of archival tissue from diagnostic tumor biopsies. - Age 18 years and older. - ECOG status of 0 or 1. - Life expectancy =12 weeks. - Subject has a prior histologically confirmed diagnosis of a grade 4 glioblastoma multiforme (GBM) or a prior histologically confirmed diagnosis of a grade 2 or 3 malignant glioma and now has radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or has a unifocal relapse of GBM. - Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy and = 12 weeks after completion of front-line radiation therapy. - Confirmed MMP2+ tumor expression by IHC (=20% moderate/high MMP2 score [2+ or 3+]). - Adequate venous access to perform leukapheresis. - No known contraindications to leukapheresis or steroids. - In-range baseline laboratory values for WBC (>2000/dL [or ANC =1000/mm^3]), platelets (=75000/mm^3), total bilirubin (=1.5xULN), AST (=2.5xULN), ALT (=2.5xULN), serum creatinine (=1.5xmg/dL), and oxygen saturation (=95% on room air) - Seronegative for human immunodeficiency virus (HIV) by antigen/antibody (Ag/Ab) testing. - Seronegative for hepatitis B and/or hepatitis C virus. - Women of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. - Agreement by women AND men of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CHM-1101. (Childbearing potential is defined as not being surgically sterilized (women and men) or, for women, having not been free from menses for > 1 year.) Exclusion Criteria: - Within 3 months of having received prior bevacizumab therapy at the time of enrollment. - Not yet recovered from toxicities of prior therapy. - Uncontrolled seizure activity and/or clinically evident progressive encephalopathy. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent. - Clinically significant uncontrolled illness. - Active infection requiring antibiotics. - Known history of HIV or hepatitis B or hepatitis C infection. - Other active malignancy. - Women only-pregnant or breastfeeding. - Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures. - Prospective subjects who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
CHM-1101 CAR-T cells
Administered via ICT/ICV dual delivery

Locations

Country Name City State
United States St. David's South Austin Medical Center - Sarah Cannon - Austin Austin Texas
United States City of Hope Medical Center Duarte California

Sponsors (1)

Lead Sponsor Collaborator
Chimeric Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Dose-limiting toxicity (DLT) Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. 28 days
Primary Cytokine Release Syndrome (CRS) Assessed per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading guideline, evaluating levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry). up tp 15 years
Primary All other adverse events and toxicities Assessed per NCI CTCAE v5.0. up to 15 years
Secondary Chimeric antigen receptor (CAR) T cell Assess levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry). up to 15 years
Secondary Endogenous T cell Assess level and phenotype detected in TCF, PB, and CSF (absolute number per µL by flowcytometry). up to15 years
Secondary Human anti-CAR antibody (HACA) Serum samples will be evaluated for HACA against the CLTX(EQ)28? therapeutic agent. up to 15 years
Secondary Progression free survival (PFS) time Measured from the date of first infusion of CAR-T cells until the first date when progressive disease (PD) is objectively documented or death from any cause, whichever is earlier. 12 months
Secondary Overall survival (OS) Measured from the date of first infusion of CAR-T cells until death. up to 15 years
Secondary Disease response Assessed by modified Response Assessment in Neuro-Oncology Criteria (RANO) criteria. 12 months
Secondary Clinical benefit rate The proportion of participants who experience a complete response, a partial response, or stable disease that is 3 months or greater in duration. 12 months
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